Addison's Disease: Symptoms, Causes, and Treatment

Addison's disease is a rare chronic condition where the adrenal glands do not produce enough essential hormones, mainly cortisol and aldosterone1 . This hormone deficiency can lead to serious health problems, including life-threatening adrenal crises if untreated2 . Although symptoms often develop slowly and can be mistaken for other conditions, early diagnosis and lifelong treatment can help patients live active, healthy lives3 .

Addison's Disease Symptoms

Symptoms of Addison's disease are often non-specific, making diagnosis challenging and frequently delayed4 . Common early symptoms include weakness, fatigue, and weight loss5 . Patients may also experience gastrointestinal complaints such as nausea, vomiting, and diarrhea6 7. Orthostatic hypotension, which causes dizziness or fainting upon standing, is another frequent symptom5 7.

A distinctive feature of Addison's disease is hyperpigmentation—darkening of the skin—which can appear as diffuse, non-scaly patches on the face, hands, and palms, and may be more noticeable inside the mouth8 9. Salt craving is also common due to aldosterone deficiency10 . Psychiatric symptoms such as depression, anxiety, social isolation, and poor concentration can occur, often linked to the gradual onset of hormone deficiency11 .

Symptoms usually progress slowly, but physical stressors like infections or injuries can worsen the condition rapidly, potentially triggering an adrenal crisis—a medical emergency characterized by severe weakness, low blood pressure, and shock4 129.

• Weakness and fatigue5 4
• Hyperpigmentation, including intraoral pigmentation8 9
• Weight loss and loss of appetite6
• Gastrointestinal symptoms: nausea, vomiting, diarrhea6 7
• Orthostatic hypotension (dizziness on standing) 57
• Salt craving10
• Psychiatric symptoms: depression, anxiety, poor concentration11
• Symptoms worsen with stress or illness4 12

Causes of Addison's Disease

Addison's disease, also called primary adrenal insufficiency, results from damage to the adrenal cortex, leading to insufficient production of cortisol and aldosterone13 . The most common cause in adults in industrialized countries is autoimmune adrenalitis, where the immune system mistakenly attacks the adrenal glands4 145. In children, congenital defects are more frequent causes4 14.

Other causes include infections such as tuberculosis, metastatic cancers invading the adrenal glands, and acquired immunodeficiency syndrome (AIDS) 57. Less common causes are adrenal hemorrhage, infiltrative diseases, and certain medications that inhibit cortisol synthesis5 7.

Risk Factors

• Autoimmune diseases (e.g., autoimmune thyroiditis, type 1 diabetes) increase risk15 16.
• Genetic predisposition to autoimmune polyendocrine syndromes16 .
• History of infections like tuberculosis or HIV5 7.
• Use of medications that suppress adrenal function (e.g., ketoconazole, etomidate) 10.
• Adrenal gland trauma or hemorrhage5 .

Diagnosing Addison's Disease

Diagnosis of Addison's disease can be difficult due to its slow onset and non-specific symptoms4 14. Blood tests are essential and typically reveal low cortisol and aldosterone levels, high adrenocorticotropic hormone (ACTH), and elevated renin levels3 17. Electrolyte imbalances such as hyponatremia (low sodium) and hyperkalemia (high potassium) are common findings3 17.

The 250 μg ACTH stimulation test is the standard diagnostic tool. It measures cortisol response after administration of synthetic ACTH; a blunted or absent increase confirms adrenal insufficiency18 . Early morning cortisol levels can also be informative, with levels above 18 μg/dL generally excluding Addison's disease16 .

Additional tests may include:

• Measurement of adrenal autoantibodies to confirm autoimmune etiology16 .
• Imaging studies such as computed tomography (CT) of the abdomen to assess adrenal gland size and detect infections, hemorrhage, or tumors3 171920.

• Insulin tolerance test or corticotropin-releasing hormone (CRH) test to differentiate primary from secondary adrenal insufficiency when needed20 .

• Low cortisol and aldosterone levels3 17

• Elevated ACTH and renin3 17
• Electrolyte disturbances: hyponatremia, hyperkalemia3 17
• Blunted cortisol response to ACTH stimulation test18
• Presence of adrenal autoantibodies in autoimmune cases16
• Imaging to evaluate adrenal gland morphology3 1719

“Addison disease is a life-threatening condition that requires accurate diagnosis and prompt treatment. A delayed diagnosis carries a high morbidity and mortality.”

— Sadaf Munir et al., StatPearls16

Addison's Disease Treatment Options

Treatment for Addison's disease involves lifelong hormone replacement therapy to substitute deficient cortisol and aldosterone3 1719. Hydrocortisone or other corticosteroids such as prednisolone are administered two to three times daily to mimic the natural circadian rhythm of cortisol secretion3 1719. Fludrocortisone is prescribed to replace aldosterone and maintain sodium and potassium balance3 1719.

Dosages often need adjustment during periods of physical stress, such as illness, surgery, or injury, to prevent adrenal crisis3 1719. In cases of adrenal crisis, immediate intravenous administration of high-dose hydrocortisone, fluids, and electrolyte replacement is critical3 1719.

Monitoring treatment includes regular assessment of symptoms, electrolytes, and blood pressure to avoid under- or overtreatment. Overreplacement with glucocorticoids may lead to complications such as obesity, diabetes, and osteoporosis15 .

• Hydrocortisone or prednisolone for cortisol replacement3 1719
• Fludrocortisone for aldosterone replacement3 1719
• Dose adjustments during stress or illness3 1719
• Emergency IV hydrocortisone and fluids for adrenal crisis3 1719
• Regular monitoring to prevent complications15

Preventing Addison's Disease

Currently, there is no evidence-based method to prevent Addison's disease, as it is primarily an autoimmune disorder22 . Early recognition and treatment of symptoms are crucial to prevent serious complications such as adrenal crisis3 17.

Patients with Addison's disease require lifelong follow-up and surveillance to manage their condition effectively3 17. Preventive strategies focus on education about stress dosing of steroids and recognizing early signs of adrenal crisis3 1719.

• Take prescribed hormone replacement medications exactly as directed3 1719
• Learn to adjust steroid doses during illness or stress3 1719
• Carry emergency hydrocortisone injection kits and medical alert identification3 1719
• Maintain regular healthcare visits for monitoring3 1719

Related Health Conditions

Addison's disease is often associated with other autoimmune disorders, such as autoimmune thyroid disease, type 1 diabetes, pernicious anemia, vitiligo, and alopecia15 16. Patients with Addison's disease have a significant risk of developing additional autoimmune conditions15 .

Improper hormone replacement therapy can lead to complications. Excess glucocorticoids may cause obesity, diabetes, and osteoporosis, while inadequate treatment increases the risk of adrenal crisis15 . Careful management by healthcare providers is essential to balance hormone levels and prevent these complications15 .

Living With Addison's Disease

“Sometimes we fall into things, and it goes a long way back to college. I was always interested in stress and stress hormones, probably trying to understand myself as a youth! This led to medical school, endocrinology, studying various aspects of the hypothalamic–pituitary–adrenal axis and ultimately now to my job at Michigan where I serve as the Millie Schembechler Professorship in Adrenal Cancer.”

— Gary Hammer, University of Michigan23

With proper treatment, patients with Addison's disease can resume normal daily activities and maintain a high functional status3 17. However, living with Addison's requires lifelong medication adherence, regular medical follow-up, and awareness of potential complications3 1719.

Patients should carry medical alert identification and have an emergency plan, including access to injectable hydrocortisone, to manage adrenal crises effectively3 1719. Dietary adjustments, such as increased salt intake during hot weather or illness, may be recommended3 1719. Calcium and vitamin D supplementation might be necessary to prevent osteoporosis related to corticosteroid use3 1719.

• Take medications consistently and as prescribed3 1719
• Wear a medical alert bracelet or carry an ID card3 1719
• Learn to recognize early signs of adrenal crisis3 1719
• Adjust medication doses during illness or stress with healthcare guidance3 1719
• Maintain a balanced diet with adequate salt, calcium, and vitamin D3 1719